Tau antisense oligomers and uses thereof

Abstract

The present invention relates to oligomer compounds (oligomers), which target Tau mRNA in a cell, leading to reduced expression of Tau protein. Reduction of Tau protein expression is beneficial for the treatment of certain medical disorders, e.g., a neurological disorder.

The invention claimed is: 
     
       1. An oligomer consisting of the nucleic acid sequence AtTTCcaaattcactTTtAC (SEQ ID NO: 473), wherein upper case letters denote beta-D-oxy-LNA, and lower case letters denote DNA monomers. 
     
     
       2. The oligomer of  claim 1 , which comprises an internucleoside linkage selected from: a phosphodiester linkage, a phosphotriester linkage, a methylphosphonate linkage, a phosphoramidate linkage, a phosphorothioate linkage, and combinations thereof. 
     
     
       3. The oligomer of  claim 1 , wherein calcium oscillations of neuronal cells which are in contact with the oligomer are greater than or equal to 95%, greater than or equal to 90%, greater than or equal to 85%, greater than or equal to 80%, greater than or equal to 75%, or greater than or equal to 70% of oscillations in a cell not in contact with the oligomer. 
     
     
       4. The oligomer of  claim 1 , which has at least one property selected from: (1) reduces expression of Tau mRNA in a cell, compared to a control cell that has not been exposed to the oligomer; and (2) reduces expression of Tau protein in a cell, compared to a control cell that has not been exposed to the oligomer. 
     
     
       5. A conjugate comprising the oligomer of  claim 1 , wherein the oligomer is covalently attached to at least one non-nucleotide or non-polynucleotide moiety. 
     
     
       6. A composition comprising the oligomer of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
       7. A kit comprising the oligomer of  claim 1  and instructions for use. 
     
     
       8. The oligomer of  claim 1 , wherein all internucleoside linkages are phosphorothioate linkages.